Phosphine-catalyzed [3 + 2] cycloaddition of allenoates with trifluoromethylketones: synthesis of dihydrofurans and tetrahydrofurans

The triphenylphosphine-catalyzed formal [3 + 2] cycloaddition of allenoates and trifluoromethylketones was realized to give the corresponding dihydrofurans in good yields with excellent γ-regioselectivities. Hydrogenation of the dihydrofurans gave 2,4,4-trisubstituted tetrahydrofurans in good yields with exclusive cis-selectivities.     

Phosphine-catalyzed dearomative [3+2] annulation of 3-nitroindoles and allenoates

The efficient phosphine-catalyzed dearomative [3+2] annulation of 3-nitroindoles with allenoates has been successfully developed, providing a facile access to cyclopenta[b]indolines with good to excellent yields and high diastereoselectivities. This strategy features mild reaction conditions, high functional group tolerance, and scalability. Additionally, the 2-nitrobenzofuran and 2-nitrobenzothiophene were good dearomative [3+2] annulation partners.     

Catalytic [2+2] and [3+2] cycloaddition reactions of allenoates with cyclic ketimines

Cyclic ketimines as electrophiles for [2+2] and [3+2] cycloaddition reactions of allenoates have been developed, affording functionalized sultam-fused azetidines and dihydropyrroles, respectively, in good yields with high regioselectivities.     

Intramolecular [4+2] cycloaddition reactions of indolylalkylpyridazines: synthesis of annulated carbazoles

Mono- and bicyclic 1,2-diazines tethered to indole dienophiles by alkylene chains were found to undergo thermally induced intramolecular Diels-Alder reactions with inverse electron demand, affording tetra- and pentacyclic condensed carbazoles.     

Thermal [3+2] cycloaddition reaction of azomethine imines with allenoates for dinitrogen-fused heterocycles

The thermal [3+2] cycloaddition reactions of two classes of azomethine imines with allenoates have been investigated. The reactions are operationally simple and proceed smoothly under mild reaction conditions to provide a variety of dinitrogen-fused heterocycles in moderate to excellent yields.     

A cyclic diphosphinite by a formal [4+4] cycloaddition reaction of β-phosphaenone

Unstable β-phosphaenones formed by reaction of the phosphanylidene-σ⁴-phosphorane DmpP = PMe₃ (Dmp = 2,6-dimesitylphenyl) with acenaphthenequinone dimerize in hexane by a formal [4+4] cycloaddition reaction to form a cyclic diphosphinite. X-ray crystallographic analysis and variable temperature ¹H NMR spectra of the cyclic diphosphinite are presented.     

Reaction of ene-bis(phosphinylallenes): [2+2] versus [4+2] cycloaddition

Reaction of ene-bis(phosphinylallenes), derived from ene-bis(propargyl alcohols) and chlorodiphenylphosphine, was investigated. Benzene-bridged bis(phosphinylallenes) exclusively gave intramolecular [2+2] cycloadducts in the presence of dimethyl fumarate in sharp contrast to the reaction of benzene-bridged bis(sulfinylallenes), which gave the corresponding [4+2] cycloadducts. On the other hand, substituted ethylene- or five-membered heterocycle-bridged bis(phosphinylallenes) provided [4+2] cycloadducts. Reaction of benzene-bridged diallene bearing both a sulfinyl group and a phosphinyl group on the two allenyl groups was also described.     

Synthesis of isoindolinones: Intramolecular [4+2] cycloaddition/retro [4+2] of pyridone propiolamides

A new synthesis of isoindolinones was discovered during a screening campaign aimed at the development of novel methods for the synthesis of pyridone-EZH2 inhibitor analogues. The reaction proceeds via an intramolecular [4+2] cycloaddition of a pyridone with a tethered propiolamide moiety followed by extrusion of isocyanic acid. The discovery, optimization, and scope of the methodology are described.     

Formal [4+2] cycloaddition of 3-phenylcyclobutanones with nitriles

Various 3-phenylcyclobutanones reacted with aliphatic and aromatic nitriles in the presence of Me₃SiOTf to afford dihydropyridones by formal [4+2] cycloaddition.     

Regioselective synthesis of 1-hydroxycarbazoles via anionic [4+2] cycloaddition of furoindolones: a short synthesis of murrayafoline-A

Suitably N-protected furoindolones react regioselectively with a variety of Michael acceptors in the presence of LDA to give 1-hydroxycarbazoles in a single-pot process and in good yields. The methodology has been applied to the synthesis of murrayafoline-A.     

Phosphine-catalyzed enantioselective [3+2] annulations of 2,3-butadienoates with imines

The first systematic screening of chiral phosphines in the cycloaddition reaction between 2,3-butadienoates and arylimines has led to the identification of fairly efficient catalysts. 2-Aryl-3-pyrrolines have been obtained with enantiomeric excesses up to 64%. In one instance, the enantiomeric excess could be increased to 91% ee by combining the enantioselective cyclization reaction with a crystallization step.     

DABCO-catalyzed [2+2] cycloaddition reactions of allenoates and trifluoromethylketones: synthesis of 2-alkyleneoxetanes

DABCO was found to be an efficient catalyst for the formal [2+2] cycloaddition reaction of allenoates and trifluoromethylketones (Paterno-Buchi reaction) to give the corresponding 2-alkyleneoxetanes in good yields with good diastereoselectivities.     

[2+2] Carbonylative cycloaddition catalyzed by palladium: stereoselective synthesis of β-lactams

[2+2] Carbonylative cycloaddition of chiral imines to various allyl halides, under CO pressure, in the presence of Et₃N, a catalytic amount of Pd(OAc)₂ and PPh₃ as ligand, are carried out. Separable diastereomeric mixtures of chiral alkenyl-β-lactams are isolated with good yields and high trans diastereoselections. Absolute configurations are assigned by X-ray measurements and ¹H NMR spectroscopy.     

Microwave-assisted iridium-catalyzed [2+2+2] cycloaddition of resin-bound dipropargylamine with alkynes

The [Ir(COD)Cl]₂/dppe system effectively catalyzes the solid-phase [2+2+2] cycloaddition of resin-bound dipropargylamine with alkynes under microwave conditions. The reaction results in high purity of isoindoline derivatives with moderate yields.     

Rhodium-catalyzed enantioselective [2+2+2] cycloaddition of diynes with unfunctionalized alkenes

A chiral rhodium complex catalyzed an enantioselective [2+2+2] cycloaddition of unsymmetrical diynes with norbornene, and tetracyclic products were obtained in good to excellent ee. The cycloaddition of a symmetrical diyne with styrene derivatives as coupling partners gave bicyclic products in good ee.     

Inverse electron-demand aza-[4+2] cycloaddition reactions of allenamides

An inverse electron-demand aza-[4+2] cycloaddition reaction of allenamides with 1-azadiene is described here. Effects of solvents on diastereoselectivity along with synthetic scopes and mechanistic insights are illustrated. Despite some synthetic limitations, this aza-[4+2] cycloaddition does provide a useful template for the synthesis of aza-glycoside related heterocycles.     

Asymmetric synthesis of azetidin-2-ones by [2+2] cycloaddition using chiral imines derived from d-(+)-glucose

Asymmetric synthesis of β-lactams by the [2+2] cycloaddition of ketenes with chiral imines derived from d-(+)-glucose was carried out; predominantly cis-β-lactams were formed with very high diastereoselectivity. The stereochemistry at C-3 and C-4 was established as 3S and 4R from the known absolute configuration of the sugar moiety.     

K3PO4 promoted dipolar [3+3] cyclization: Direct synthesis of pyrazino[2,1-a]isoquinoline derivatives

A K₃PO₄ promoted dipolar [3+3] cyclization of dihydroisoquinoline imines and arylacyl bromides has been developed. This process realized the direct synthesis of pyrazino[2,1-a]isoquinoline derivatives in 44–69% yields. A head to tail dimerization was proposed as key step for this procedure.